{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338949/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338949"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Impaired synthesis of both telomere strands and adaptive TERT reduction in RTEL1 ATPase-dead cells","description":"Regulator of Telomere Elongation Helicase 1 (RTEL1) plays a critical role in telomere replication by disassembling DNA secondary structures such as G-quadruplexes and telomeric loops (T-loops). However, its precise mechanism remains unclear. Previously, we generated HeLa cells homozygous for ATPase-dead RTEL1. Here, we found that these cells have a 50-60% reduction in the synthesis of both telomere strands, indicating that RTEL1 ATPase activity is essential for replicating both leading and lagging telomeric DNA. Surprisingly, these cells also showed a substantial reduction in Telomerase Reverse Transcriptase (TERT) mRNA levels and a 60-80% reduction in telomerase activity, without activating alternative lengthening of telomeres (ALT). Forced TERT overexpression suppressed proliferation and caused late S/G2 accumulation, implying that the natural TERT reduction provides adaptive resistance. Expressing wild-type (WT) RTEL1 at levels close to physiological levels failed to rescue growth defects, suggesting a dominant-negative effect. These results reveal unexpected interactions between RTEL1 and telomerase and show how cancer cells compensate for RTEL1 dysfunction by decreasing TERT expression.","dates":{"publication":"2026/07/24"},"accession":"GSE338949","cross_references":{"GSM":["GSM9885457","GSM9885456","GSM9885459","GSM9885458","GSM9885460","GSM9885451","GSM9885462","GSM9885461","GSM9885453","GSM9885452","GSM9885455","GSM9885454"],"GPL":["34284"],"GSE":["338949"],"taxon":["Homo sapiens"]}}